Abstract 916: A novel LAP-IL2 fusion protein elicits efficacy as single agent in syngeneic renal and melanoma mouse models
| Autor: | Maria E. Riveiro, David Gould, Keyvan Rezai, Giulia Taraboletti, Yuti Chernajovsky, Marina Meroni, Massimo Russo, Patrizia Borsotti, Roberta Frapolli, Christopher Schultz |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Cancer Research. 81:916-916 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Background. Recombinant IL-2 (rIL-2; aldesleukin) has consistently shown single agent responses and survival benefits in metastatic melanoma and renal cell carcinoma. However, severe toxic side effects associated with high doses, as well as the poor PK profile of rIL-2, have limited its clinical usage. Stealthyx generated a new compound linking the Latency Associated Peptide (LAP) of TGF-β precursor to IL-2 via a metalloproteinase (MMP) cleavage site, providing a protective shell-like structure around IL-2. This structure increases its half-life and warrants release of IL-2 at sites of high MMP activity thus avoiding systemic side effects. Here we have evaluated the efficacy and tolerability of the novel construct LAP (mut) IL-2 T pep in mice bearing subcutaneous melanoma (B16-BL6) or renal carcinoma (RENCA) compared to equimolar rIL-2 doses. Materials and Methods. B16-BL6 cells were injected s.c. in the flank of C57BL/6 mice and RENCA cells were injected s.c in BALB/c mice. Once tumor masses reached about 50 mg mice were randomized to receive LAP (mut) IL-2 T (2.7-0.54 mg/kg i.p.), rIL-2 (300000 UI/mouse), their combination with anti-PD1 antibody (250 μg/mouse) or the irrelevant (250 μg/mouse). Four hours after the 9th dose of construct, mice were sacrificed to collect plasma and tumors. Tumor CD3 infiltration was evaluated by IHC. Plasma cytokines were measured with Luminex technology Milliplex MCYTOMAG-70K with Bio-Plex Multiplex (BioRad). Results. LAP (mut) IL-2 T pep at 2.7 mg/kg displayed anti-tumor activity (best T/C = 57% at day 16 after inoculum, p Conclusion. These results show that LAP(mut) IL-2 T pep is well tolerated and has anti-tumor efficacy against the B16-BL6 preclinical model, with a different profile of systemic activity on cytokines compared to rIL-2. Citation Format: Maria Eugenia Riveiro, Roberta Frapolli, Giulia Taraboletti Giulia Taraboletti, Keyvan Rezai, Marina Meroni, Massimo Russo, Patrizia Borsotti, Chris Schultz, David Gould, Yuti Chernajovsky. A novel LAP-IL2 fusion protein elicits efficacy as single agent in syngeneic renal and melanoma mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 916. |
| Databáze: | OpenAIRE |
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